Yonsei Med J.  2021 Mar;62(3):224-230. 10.3349/ymj.2021.62.3.224.

Genetic Analysis of Korean Adult Patients with Nontuberculous Mycobacteria Suspected of Primary Ciliary Dyskinesia Using Whole Exome Sequencing

• Cho EH
• Ki CS
• Yun SA
• Kim SY
• Jhun BW
• Koh WJ
• Huh HJ
• Lee NY

• KMID: 2513213
• DOI: http://doi.org/10.3349/ymj.2021.62.3.224

Abstract

Purpose
Nontuberculous mycobacteria (NTM) is ubiquitous in the environment, but NTM lung disease (NTM-LD) is uncommon. Since exposure to NTM is inevitable, patients who develop NTM-LD are likely to have specific susceptibility factors, such as primary ciliary dyskinesia (PCD). PCD is a genetically heterogeneous disorder of motile cilia and is characterized by chronic respiratory tract infection, organ laterality defect, and infertility. In this study, we performed whole exome sequencing (WES) and investigated the genetic characteristics of adult NTM patients with suspected PCD.
Materials and Methods
WES was performed in 13 NTM-LD patients who were suspected of having PCD by clinical symptoms and/or ultrastructural ciliary defect observed by transmission electron microscopy. A total of 45 PCD-causing genes, 23 PCDcandidate genes, and 990 ciliome genes were analyzed.
Results
Four patients were found to have biallelic loss-of-function (LoF) variants in the following PCD-causing genes: CCDC114, DNAH5, HYDIN, and NME5. In four other patients, only one LoF variant was identified, while the remaining five patients did not have any LoF variants.
Conclusion
At least 30.8% of NTM-LD patients who were suspected of having PCD had biallelic LoF variants, and an additional 30.8% of patients had one LoF variant. Therefore, PCD should be considered in patients with NTM-LD with symptoms or signs suspicious of PCD.

Keyword

Primary ciliary dyskinesia; nontuberculous mycobacteria; whole exome sequencing